Deeper insight into ferroptosis: association with Alzheimer's, Parkinson's disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis

Abstract

Ferroptosis is an emerging and novel type of iron-dependent programmed cell death which is mainly caused by the excessive deposition of free intracellular iron in the brain cells. This deposited free iron exerts a ferroptosis pathway, resulting in lipid peroxidation (LiPr). There are mainly three ferroptosis pathways viz. iron metabolism-mediated cysteine/glutamate, and LiPr-mediated. Iron is required by the brain as a redox metal for several physiological activities. Due to the iron homeostasis balance disruption, the brain gets adversely affected which further causes neurodegenerative diseases (NDDs) like Parkinson's and Alzheimer's disease, strokes, and brain tumors like glioblastoma (GBS), and glioma. Nanotechnology has played an important role in the prevention and treatment of these NDDs. A synergistic effect of nanomaterials and ferroptosis could prove to be an effective and efficient approach in the field of nanomedicine. In the current review, the authors have highlighted all the latest research in the field of ferroptosis, specifically emphasizing on the role of major molecular key players and various mechanisms involved in the ferroptosis pathway. Moreover, here the authors have also addressed the correlation of ferroptosis with the pathophysiology of NDDs and theragnostic effect of ferroptosis and nanomaterials for the prevention and treatment of NDDs.

Keywords: Ferroptosis; Parkinson’s disorder; glioblastoma; glutathione; neurodegenerative.

Figure 1.

Mechanism pathways of ferroptosis adapted from [16].

Figure 2.

Cystine/glutamic acid-mediated ferroptosis pathway.

Figure 3.

Ferroptosis mechanism pathways adapted from [14].

Figure 4.

Hallmarks features of ferroptosis.

Figure 5.

Various markers of ferroptosis.

Figure 6.

Mechanisms of NPs-induced ferroptosis. (a) Membrane impairment induced by NPs involving LiPr and inactivation of system xc-; (b) lysosome dysfunction induced by NPs including disruption of lysosomal membrane, alteration of acidic environment, modification of STEAP3 and DMT1 activities; and (c) mitochondrial damage induced by NPs including destruction of mitochondrial morphology and dysregulation of the mitochondrial antioxidant defense as well as iron dyshomeostasis.

Figure 7.

Putative pathway for ferroptosis participates in neuroinflammation to NDDs reprinted from [16].

Figure 8.

Signalling pathways of ferroptosis and associated NDDs.